Tests of the effects of acute and chronic administration of caffeine on autonomic nervous system (ANS) functioning have been carried out to evaluate the role of ANS activity in behavioral and subjective effects of this drug. A test of attention using a reaction time method is included. The test protocol involves recording peripheral indicators of ANS activity such as skin conductance (SC), heart rate (HR), and skin temperature during a session consisting of a rest period, presentation of a series of simple tones to which no response is required, and the reaction time task. Studies have been carried out on the effects of the acute administration of two doses of caffeine and a placebo in 6-13 year old boys and in men, and a pilot study and major study of chronic (2 week) caffeine intake in children. Results of the acute studies showed dose-dependent increases in such SC indices of arousal as frequency of spontaneous fluctuations and SC level along with retarded habituation of SC responses to the simple tones. HR showed a significant decrease after the low doses of caffeine and a partial return to the placebo level after the high dose. Results of our recent dose study on 41 boys and girls are similar for the SC variables, and there was a trend for decreased HR on caffeine. The recent study confirmed the earlier ones in showing that while on placebo, subjects who were frequent caffeine consumers had lower SC arousal indices than non-consumers. These results, like those for caffeine effects, tended to be congruent with subjective reports of anxiety-like symptoms. The SC effects of caffeine are much like those seen in patients with anxiety states and in normals after taking dextroamphetamine. However, HR results differ. These studies suggest that ANS activity and associated subjective states may play a role in the dietary choice of caffeine.